Atypical Antipsychotic Agents (Includes Invega) ↔ Dementia

Severe Potential Hazard, High plausibility

Applies to: Dementia

Elderly patients with dementia- related psychosis treated with antipsychotic drugs are at an increased risk of death, mostly from cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) causes. A causal relationship with antipsychotic use has not been established. In controlled trials, treatment with some atypical antipsychotic drugs was also associated with an increased risk of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, in elderly patients with dementia- related psychosis. These agents are not approved for the treatment of patients with dementia- related psychosis.

Major

Neuroleptics (Includes Invega) ↔ Nms

Severe Potential Hazard, High plausibility

Applies to: Neuroleptic Malignant Syndrome

The central dopaminergic blocking effects of neuroleptic agents may precipitate or aggravate a potentially fatal symptom complex known as neuroleptic malignant syndrome (NMS). NMS is observed most frequently when high-potency agents like haloperidol are administered intramuscularly, but may occur with any neuroleptic agent given for any length of time. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria, and acute renal failure. Neuroleptic agents should not be given to patients with active NMS and should be immediately discontinued if currently being administered in such patients. In patients with a history of NMS, introduction or reintroduction of neuroleptic agents should be carefully considered, since NMS may recur.

Neuroleptics (Includes Invega) ↔ Tardive Dyskinesia

Severe Potential Hazard, High plausibility

Applies to: Tardive Dyskinesia

Neuroleptic agents may precipitate symptoms of tardive dyskinesia (TD), a syndrome consisting of rhythmic involuntary movements variously involving the tongue, face, mouth, lips, jaw, and/or trunk and extremities, following chronic use of at least several months but often years. Elderly patients, particularly women, are most susceptible. Both the risk of developing the syndrome and the likelihood that it will become irreversible increase with the duration and total cumulative dose of neuroleptic therapy administered. However, patients may infrequently develop symptoms after relatively brief treatment periods at low dosages. If TD occurs during neuroleptic therapy, prompt withdrawal of the offending agent or at least a lowering of the dosage should be considered. TD symptoms may become more severe after drug discontinuation or a dosage reduction, but may gradually improve over months to years. In patients with preexisting drug-induced TD, initiating or increasing the dosage of neuroleptic therapy may temporarily mask the symptoms of TD but could eventually worsen the condition. The newer, atypical neuroleptic agents (e.g., risperidone, quetiapine, olanzapine) tend to be associated with a substantially reduced risk of inducing TD and are considered the drugs of choice in patients being treated for psychosis.

Antidepressant/Antipsychotic Agents (Includes Invega) ↔ Depression

Moderate Potential Hazard, Moderate plausibility

Applies to: Depression, Bipolar Disorder

Adult and pediatric patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset.

Moderate

Antipsychotic Agents (Includes Invega) ↔ Aspiration

Moderate Potential Hazard, Moderate plausibility

Applies to: Dysphagia

Esophageal dysmotility and aspiration have been associated with the use of antipsychotic drugs. These drugs should be administered cautiously in patients at risk for aspiration pneumonia.

Moderate

Antipsychotic Agents (Includes Invega) ↔ Seizure

Moderate Potential Hazard, Moderate plausibility

Applies to: Seizures, Head Injury, Alcoholism

Antipsychotic drugs can lower the seizure threshold and trigger seizures in a dose-dependent manner. This risk is greatest in patients with a history of seizures or with conditions that lower the seizure threshold. Therapy with Antipsychotic drugs should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism.

Cases of leukopenia, neutropenia, and agranulocytosis have been reported with the use of atypical antipsychotic agents. Patients with preexisting low white blood cell count may be at increased risk. Therapy with these agents should be administered cautiously in patients with a history of, or predisposition to, decreased white blood cell or neutrophil counts. Clinical monitoring of hematopoietic function is recommended. At the first sign of a clinically significant decline in white blood cells, discontinuation of atypical antipsychotic therapy should be considered in the absence of other causative factors, and the patient closely monitored for fever or other signs and symptoms of infection.

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported with the use of atypical antipsychotic agents. Patients with diabetes should be monitored for worsening control of blood glucose when treated with these agents. It is recommended that patients with risk factors for diabetes mellitus starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment, and periodically thereafter. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when treatment with these agents was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the atypical antipsychotic drug.

The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

Moderate

Atypical Antipsychotic Agents (Includes Invega) ↔ Lipid Alterations

Moderate Potential Hazard, Moderate plausibility

Applies to: Hyperlipidemia

Atypical antipsychotic drugs have been associated with undesirable alterations in lipid levels. While all agents in the class have been shown to produce some changes, each drug has its own specific risk profile. Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment.

Moderate

Atypical Antipsychotic Agents (Includes Invega) ↔ Priapism

Atypical antipsychotic agents with alpha-adrenergic blocking effects may cause priapism. The condition is characterized by prolonged, often painful erections lasting longer than 4 hours. If not treated promptly, priapism can cause irreversible damage to the erectile tissue. Therapy with these agents should be administered cautiously in patients with a history of priapism, conditions that may predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, leukemia, thalassemia), or anatomical deformations of the penis (e.g., angulation, cavernosal fibrosis, Peyronie's disease). Patients who experience an erection lasting longer than 4 hours, whether painful or not, should immediately discontinue the drug and seek emergency medical attention.

Moderate

Atypical Antipsychotic Agents (Includes Invega) ↔ Qt Prolongation

Some atypical antipsychotic agents can prolong the QTc interval of the electrocardiogram in a dose-dependent manner. Electrolyte disturbances such as hypokalemia and hypomagnesemia may augment the prolongation effect of these agents on the QT interval and should be corrected prior to institution of therapy. In addition, patients who experience frequent, severe, or prolonged diarrhea may be subject to electrolyte losses and should be followed closely and managed accordingly during therapy with these agents. Atypical antipsychotic agents should be avoided in patients with a history of cardiac arrhythmias or other conditions that may increase the risk of torsade de pointes and/or sudden death, including bradycardia; hypokalemia or hypomagnesemia; and congenital long QT syndrome.

Moderate

Atypical Antipsychotic Agents (Includes Invega) ↔ Weight Gain

Moderate Potential Hazard, Moderate plausibility

Applies to: Obesity

Weight gain has been observed with atypical antipsychotic use. While all agents in the class have been shown to produce some changes, each drug has its own specific risk profile. When treating pediatric patients with atypical antipsychotic agents, weight gain should be monitored and assessed against that expected for normal growth. Monitor weight at baseline and frequently thereafter.

Moderate

Neuroleptics (Includes Invega) ↔ Hyperprolactinemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Hyperprolactinemia, Breast Cancer

The chronic use of neuroleptic agents can cause persistent elevations in prolactin levels due to antagonism of dopamine D2 receptors. Based on in vitro data, approximately one-third of human breast cancers are thought to be prolactin-dependent. The clinical significance of this observation with respect to long-term neuroleptic therapy is unknown. Chronic administration of neuroleptic drugs has been associated with mammary tumorigenesis in rodent studies but not in human clinical or epidemiologic studies. Until further data are available, therapy with neuroleptic agents should be administered cautiously in patients with a previously detected breast cancer. Caution is also advised in patients with preexisting hyperprolactinemia. Hyperprolactinemia may suppress hypothalamic gonadotrophin releasing hormone (GnRH), resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds; however, the clinical significance of elevated serum prolactin levels is unknown for most patients. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male patients.

Neuroleptics (Includes Invega) ↔ Seizure Disorders

Moderate Potential Hazard, Moderate plausibility

Applies to: Alcoholism, CNS Disorder

Neuroleptic agents can lower the seizure threshold and induce seizures, particularly when dosages are high or increased rapidly and during the initiation of therapy. Clozapine appears to have the greatest epileptogenic potential, while most of the other newer, atypical neuroleptic agents (e.g., risperidone, quetiapine, olanzapine), as well as haloperidol and molindone, have the least. Therapy with neuroleptic agents should be administered cautiously in patients with a history of seizures or other factors predisposing to seizures such as abnormal EEG, preexisting CNS pathology, or head trauma. Adequate anticonvulsant therapy should be maintained during administration of neuroleptic agents. Clozapine should not be used in patients with uncontrolled epilepsy.

Paliperidone (Includes Invega) ↔ Antiemetic Effect

An antiemetic effect was observed in preclinical studies with paliperidone. This effect, if it occurs in humans, may mask the signs and symptoms of overdosage with certain drugs or of conditions such as intestinal obstruction, Reye's syndrome, and brain tumor. Cautions should be exercised when given paliperidone to these patients.

Moderate

Paliperidone (Includes Invega) ↔ Gastrointestinal Obstruction

Moderate Potential Hazard, Moderate plausibility

Applies to: Gastrointestinal Obstruction

There have been rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of drugs in non-deformable controlled-release formulations. Because paliperidone extended-release tablets are non-deformable and do not appreciably change in shape in the gastrointestinal tract, paliperidone extended-release tablets should ordinarily not be administered to patients with pre-existing severe gastrointestinal narrowing, pathologic or iatrogenic.

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